Ovarian sympathetic neural activity can cause or exacerbate several ovarian conditions, including, but not limited to, polycystic ovary syndrome, infertility, and dysfunctional hormone or steroid production. Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive ages (e.g., 12-45 years old). Symptoms of PCOS can include oligoovulation or anovulation resulting in irregular menstruation, amenorrhea, ovulation-related infertility, and enlarged or polycystic ovaries. Other symptoms include excess of androgenic hormones (e.g., testosterone) which can result in acne and hirsutism. Clinical complications, such as insulin resistance, obesity, Type 2 diabetes, high cholesterol, and hypertension can also be common in PCOS patients. Further complications can include development of endometrial cancer or breast cancer. Most prescribed treatments address specific manifestations of PCOS and do not address underlying causes of the disease. Moreover, many of these treatments only address specific sequelae individual symptoms or indications) of the disease, and patients can be required to combine multiple treatment programs for treating these conditions and/or complications separately. For example, androgen excess and associated symptoms (e.g., hirsutism, acne) are commonly treated with estrogen-progestin contraceptives, antiandrogens, anti-acne treatments, and prescription drugs and over-the-counter depilatories for removing or slowing unwanted hair growth. Additionally, anovulation and fertility issues are treated with ovulation promoting drugs (e.g., clomiphene or follicle stimulating hormone (FSH) injections) or in vitro fertilization. Other treatments are prescribed for PCOS patients having hypertension (e.g., anti-hypertensive medications), hyperlipidemia (e.g., statins, other cholesterol lowering agents), and insulin resistance/Type 2 diabetes (e.g., metformin, other diabetic medications). Such pharmacologic strategies, however, have significant limitations including limited efficacy, side effects, long-term maintenance regimens and others.
The sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Fibers of the SNS extend through tissue in almost every organ system of the human body. For example, some fibers extend from the brain, intertwine along the aorta, and branch out to various organs. As groups of fibers approach specific organs, fibers particular to the organs can separate from the groups. Signals sent via these and other fibers can affect characteristics such as pupil diameter, gut motility, and urinary output. Such regulation can have adaptive utility in maintaining homeostasis or in preparing the body for rapid response to environmental factors. Chronic activation of the SNS, however, is a common maladaptive response that can drive the progression of many disease states. Excessive activation of the ovarian SNS has been identified experimentally and in humans as a likely contributor to the complex pathophysiology of PCOS. As examples, studies measuring efferent postganglionic muscle sympathetic nerve activity (MSNA) in PCOS patients revealed that PCOS is associated with high MSNA. Elevated testosterone and cholesterol lipid levels were identified as independent predictors of MSNA in PCOS. Involvement of the SNS in PCOS can be further characterized by finding that there is a greater density of catecholaminergic nerve fibers in polycystic ovaries and altered peripheral catecholamine secretion in adolescent PCOS patients. It is also known that activation of the sympathetic neurons innervating the ovary precedes the development of cystic ovaries in rats.